2-(4-((3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)methyl)phenoxy)ethyl 4-methylbenzenesulfonate | 1396802-75-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-(4-((3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)methyl)phenoxy)ethyl 4-methylbenzenesulfonate
• 英文别名: 2-[4-(spiro[1H-2-benzofuran-3,4'-piperidine]-1'-ylmethyl)phenoxy]ethyl 4-methylbenzenesulfonate
• CAS: 1396802-75-7
• 化学式: C₂₈H₃₁NO₅S
• 分子量: 493.624
• InChiKey: DBCZZDYFYMFSIM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  73.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(4-((3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)methyl)phenoxy)ethyl 4-methylbenzenesulfonate 在 potassium carbonate 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 、 氢氟酸 作用下， 以 水 、 乙腈 为溶剂， 反应 0.08h， 生成 C₂₁H₂₄⁽¹⁸⁾FNO₂
  参考文献：
  名称：

  Synthesis and Evaluation of Novel ¹⁸F-Labeled Spirocyclic Piperidine Derivatives as σ₁ Receptor Ligands for Positron Emission Tomography Imaging

  摘要：

  A series of spirocyclic piperidine derivatives were designed and synthesized as sigma(1) receptor ligands. In vitro competition binding assays showed that 1'-(4-(2-fluoroethoxy)benzyl)-3H-spiro[2-benzofuran-1,4'-pipericline] (19) possessed high sigma(1) receptor affinity (K-i = 0.79 nM) and excellent sigma(1)/sigma(2) subtype selectivity (350-fold) as well as high sigma(1)/VAChT selectivity (799-fold). The radiolabeled compound [F-18]19 was synthesized by substitution of the tosylate precursor 24 with [F-18]fluoride, with an isolated radiochemical yield of 35-60%, a radiochemical purity of >99%, and a specific activity of 30-55 GBq/mu mol. Biodistribution studies in imprinting control region mice indicated that [F-18] 19 displayed excellent initial brain uptake and slow washout. Ex vivo autoradiography in Sprague Dawley rats demonstrated high accumulation of the radiotracer in brain areas known to express high levels of sigma(1) receptors. Micro positron emission tomography imaging and blocking studies confirmed the specific binding of [F-18] 19 to sigma(1) receptors in vivo.

  DOI：

  10.1021/jm301734g
• 作为产物：
  描述：

  3H-螺[2-苯并呋喃-1,4'-哌啶] 在 potassium carbonate 作用下， 以 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 20.0h， 生成 2-(4-((3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)methyl)phenoxy)ethyl 4-methylbenzenesulfonate
  参考文献：
  名称：

  Synthesis and Evaluation of Novel ¹⁸F-Labeled Spirocyclic Piperidine Derivatives as σ₁ Receptor Ligands for Positron Emission Tomography Imaging

  摘要：

  A series of spirocyclic piperidine derivatives were designed and synthesized as sigma(1) receptor ligands. In vitro competition binding assays showed that 1'-(4-(2-fluoroethoxy)benzyl)-3H-spiro[2-benzofuran-1,4'-pipericline] (19) possessed high sigma(1) receptor affinity (K-i = 0.79 nM) and excellent sigma(1)/sigma(2) subtype selectivity (350-fold) as well as high sigma(1)/VAChT selectivity (799-fold). The radiolabeled compound [F-18]19 was synthesized by substitution of the tosylate precursor 24 with [F-18]fluoride, with an isolated radiochemical yield of 35-60%, a radiochemical purity of >99%, and a specific activity of 30-55 GBq/mu mol. Biodistribution studies in imprinting control region mice indicated that [F-18] 19 displayed excellent initial brain uptake and slow washout. Ex vivo autoradiography in Sprague Dawley rats demonstrated high accumulation of the radiotracer in brain areas known to express high levels of sigma(1) receptors. Micro positron emission tomography imaging and blocking studies confirmed the specific binding of [F-18] 19 to sigma(1) receptors in vivo.

  DOI：

  10.1021/jm301734g

文献信息

• Synthesis and Evaluation of Novel ¹⁸F-Labeled Spirocyclic Piperidine Derivatives as σ₁ Receptor Ligands for Positron Emission Tomography Imaging
  作者：Yan Li、Xia Wang、Jinming Zhang、Winnie Deuther-Conrad、Fang Xie、Xiaojun Zhang、Jian Liu、Jinping Qiao、Mengchao Cui、Jörg Steinbach、Peter Brust、Boli Liu、Hongmei Jia

  DOI：10.1021/jm301734g

  日期：2013.5.9

  A series of spirocyclic piperidine derivatives were designed and synthesized as sigma(1) receptor ligands. In vitro competition binding assays showed that 1'-(4-(2-fluoroethoxy)benzyl)-3H-spiro[2-benzofuran-1,4'-pipericline] (19) possessed high sigma(1) receptor affinity (K-i = 0.79 nM) and excellent sigma(1)/sigma(2) subtype selectivity (350-fold) as well as high sigma(1)/VAChT selectivity (799-fold). The radiolabeled compound [F-18]19 was synthesized by substitution of the tosylate precursor 24 with [F-18]fluoride, with an isolated radiochemical yield of 35-60%, a radiochemical purity of >99%, and a specific activity of 30-55 GBq/mu mol. Biodistribution studies in imprinting control region mice indicated that [F-18] 19 displayed excellent initial brain uptake and slow washout. Ex vivo autoradiography in Sprague Dawley rats demonstrated high accumulation of the radiotracer in brain areas known to express high levels of sigma(1) receptors. Micro positron emission tomography imaging and blocking studies confirmed the specific binding of [F-18] 19 to sigma(1) receptors in vivo.